Multicomponent gummy compositions with hard core

ABSTRACT

The present disclosure provides oral, chewable dosage forms that are suitable for delivery of one or more active ingredients to a consumer, particularly a human individual. The dosage forms can be configured as multicomponent compositions formed of: a first component including a gummy composition; a second component that is a particulate material or is a pre-formed solid unit or plurality of pre-formed solid units; and an active ingredient. The second component can be, for example, in the form of a pharmaceutically acceptable oral dosage unit, such as a tablet, a caplet, a soft shell capsule, a hard shell capsule, a microcapsule, or a pastille.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.15/092,283, filed Apr. 6, 2016, which claims priority to U.S.Provisional Patent Application Nos. 62/238,947, filed Oct. 8, 2015 and62/144,224, filed Apr. 7, 2015, the disclosures of which areincorporated here by reference in their entirety.

FIELD OF THE DISCLOSURE

The present disclosure relates to orally ingestible dosage forms. Thedosage forms can comprise at least two different compositions include amulticomponent unit in a variety of combinations.

BACKGROUND

Oral dosing of many materials with desirable properties and functionscan be problematic when provided in a chewable form because theintrinsic taste of such materials can be unpleasant, particularly tochildren. The intrinsic bitterness of certain active pharmaceuticalingredients (APIs) in particular can present a major obstacle to theacceptance, compliance, and effectiveness of treatments including oral,chewable dosing.

Previous approaches to addressing the problem of poor palatability ofcertain materials have been based mainly on nullifying undesirabletastes using flavor additives, chemical chelation (e.g., using ionexchange resins and β-cyclodextrins) and physical encapsulation. Thesesystems can be adapted into solid dosage forms or liquid basedformulations as solutions, suspensions, or multi-phase emulsions.

Generally, most children cannot swallow traditional solid dosage forms(e.g., tablets and capsules) at least until the age of six due to therisk of choking. For young children (i.e., <2 years of age), liquiddosage forms are preferred as dosing can be facilitated via an oralsyringe or spoon. These dosage forms, however, can be problematic asthey accentuate the taste issue of bitter active ingredients insolution. Suspensions can improve taste-masking effectiveness, however,mouth feel and grittiness is often the overriding issue.

Alternative non-liquid formulations have been designed to compensate forthe poor dosing acceptability and taste limitation of liquid-basedformulations for older children (>2 years of age). These formulationstypically can include chewable tablets, gummies, specially compoundedlollipops, and other confectionary mimics.

Gummy dosage forms are particularly effective for enabling compliantdosing in children as they provide a palatable, chewable base and canincorporate active ingredient(s) that are generally of very low dose,have the ability to withstand the high thermal stress of the gummymanufacturing process, and have low intrinsic taste response. Moreover,while gummy dosage forms provide the basis for effective dosing ofactive ingredients to children, their application for the delivery ofAPIs and like materials has been highly restrictive due to the limitednumber of active ingredients that are compatible with the gummy dosageplatform.

Gummy dosage forms have previously been produced by compounding avariety of ingredients (e.g., sugars, corn syrup, water, gelatin,flavors, and other sweeteners) then cooking the mixture at hightemperatures (e.g., up to about 240° C.) before depositing the cookedmixture into preformed molds. The incorporation of the activeingredients can be facilitated only during the initial compounding stepprior to cooking. The viscosity of the cooked mixture is generally toohigh to enable the active ingredients to be added retrospectively. As aresult of the very high thermal stress of the cooking process, theactive ingredients can be subject to significant chemical and/orphysical degradation during the manufacture of gummies. Accordingly, thepractice of utilizing overages (including excess active ingredient tooff-set the losses due to degradation during manufacturing) has beeninstituted.

The use of overages to off-set gross manufacturing losses in gummydosage forms is permitted only for some functional actives that do notpresent safety concerns. The application of this practice for APIs isnot generally feasible as it may lead to significant efficacy, safety,and regulatory issues. In addition, as the quality control requirementsfor APIs (i.e., claimed dose of active, content uniformity, degradationlimits, etc.) are generally much more stringent than food-basedfunctional additives, the suitability of gummies as an oral deliveryplatform becomes even more prohibitive. As such, there remains a need inthe art for oral, chewable dosage forms suitable for delivery of APIsand the like in a manner where active ingredient content can be closelycontrolled throughout manufacturing to provide a resulting dosage formof consistent quality and desirable palatability.

SUMMARY OF THE DISCLOSURE

The present disclosure provides chewable, multicomponent dosage formsthat are adapted for the delivery of a wide variety of activeingredients to individuals that may have difficulty in swallowingconventional oral dosage forms (e.g., children and geriatric adults)and/or those who have an aversion to the taste of the active ingredientsor have dosing fatigue to swallowable pills. The present disclosureprovides for formulations of active ingredients in dosage forms that arestable during storage under ambient conditions and have improvedpalatability attributes over conventional oral dosage forms, such asconventional tablets and capsules.

In one or more embodiments, a multicomponent composition according tothe present disclosure can be configured for oral administration, andcan particularly provide improved palatability for an active ingredientthat can be included in the composition. For example, the multicomponentcomposition can comprise: a first component that is a gummy composition;a second component that is in the form of a particulate material or is apre-formed solid unit or plurality of pre-formed units; and an activeingredient. In some embodiments, the first component can comprise atleast a portion of an outer surface of the multicomponent composition.In further embodiments, the second component can comprise at least aportion of the outer surface of the multicomponent composition.

A multicomponent composition according to the present disclosure can befurther defined in relation to one or more of the following statements,which statements can be combined in any number and order.

The first component can completely surround the second component suchthat the first component is substantially a shell surrounding at leastone core formed of the second component.

The multicomponent composition can further comprise a third componentconfigured as a layer between the first component and the secondcomponent.

The third component can be configured as a barrier layer thatsubstantially prevents passage of water between the first component andthe second component.

The second component can comprise a plurality of units.

The active ingredient can be included in the second component.

The active ingredient can be included in the first component.

The active ingredient can be a natural or synthetic substance that isrecognized as being beneficial to human health.

The active ingredient can be selected from the group consisting ofnon-steroidal anti-inflammatory drugs (NSAIDs), analgesics,antihistamines, decongestants, expectorants, antitussives, sleep aids,antibiotics, laxatives, anti-diarrheals, anthelmintics, antacids,vitamins, minerals, phytonutrients, fiber, fatty acids, amino acids,polypeptides, botanicals, herbs, prebiotics, probiotics, andcombinations thereof.

The gummy composition can be elastic or viscoelastic.

The gummy composition can comprise about 70% to about 94% w/w of one ormore hydrophilic bulking agents, about 1% to about 20% w/w of the one ormore hydrophilic, long-chain polymers, and about 5% to about 35% w/w ofa water source.

The one or more bulking agents can comprise one or more saccharides orsaccharide derivatives.

The one or more bulking agents can comprise one or more hydrogenatedcarbohydrates.

The one or more hydrophilic bulking agents can include one or both ofsugar solids and granulated sugar.

The one or more hydrophilic bulking agents can include glucose, sucrose,and sorbitol.

The active ingredient can be in an encapsulated form.

The composition in the form of a compressed solid can comprise one ormore ingredients selected from the group consisting of saccharides,saccharide derivatives, lipids, cellulosic polymers, cellulosic polymerderivatives, inorganic salts, and combinations thereof.

The second composition is a pre-formed solid unit or plurality of unitsin the form of one or more of a tablet, a caplet, a hard shell capsule,a soft shell capsule, a microcapsule, and a pastille.

The second composition is a pre-formed tablet having a hardness of about2 Kp to about 35 Kp.

The pre-formed tablet can be orally disintegrable or dissolvable.

The pre-formed tablet can have a hardness of about 4 Kp to about 20 Kp.

The pre-formed tablet can comprise about 5% to about 80% w/w of one ormore bulking agents, about 0.1% to about 15% w/w of one or moredisintegrants, about 0.05% to about 5% w/w of one or more processingaids, and the active ingredient in an amount of about 0.1% to about 60%w/w.

The pre-formed tablet can be stable such that the active ingredientexhibits substantially no degradation when the core composition isstored for a time of 20 days at a temperature of 40° C. and a relativehumidity of 75%.

The pre-formed tablet can be stable such that, separate from the firstcomponent, the pre-formed tablet absorbs less than about 5% by weight ofwater (based on the weight of the tabletted composition) over a time of14 days at a temperature of 40° C. and a relative humidity of 75%.

The pre-formed tablet can have a maximum dimension of about 6 mm toabout 12 mm.

The pre-formed tablet can have a diameter of about 6 mm to about 12 mmand a thickness of about 0.5 mm to 8 mm.

The pre-formed tablet can have a maximum dimension of about 2 mm toabout 10 mm.

The pre-formed tablet can have a diameter of about 2 mm to about 10 mmand a thickness of about 0.5 mm to 6 mm.

The pre-formed tablet, prior to combination with the first component,can be friable and have a brittleness index of about 0.5 to about 0.95.

The second composition is a pre-formed unit of a chewy compositionhaving a hardness of about 4 Kp to about 20 Kp.

The pre-formed unit of the chewy composition can comprise about 10% toabout 60% w/w of one or more bulking agents, about 5% to about 60% w/wof one or more hydrophilic polymers, about 0.05% to 5% of one or moreprocessing aids, optionally one or more disintegrants, and the activeagent in an amount of about 0.1% to about 60% w/w.

The pre-formed unit of the chewy composition can be water stable suchthat, separate from the first component, the pre-formed unit of thechewy composition absorbs less than about 10% by weight of water (basedon the weight of the chewy composition) over a time of 5 days at atemperature of 40° C. and a relative humidity of 75%.

The pre-formed unit of the chewy composition can be stable such that theactive ingredient exhibits substantially no degradation when the chewycomposition is stored for a time of 11 days at a temperature of 40° C.and a relative humidity of 75%.

The pre-formed unit of the chewy composition can have a maximumdimension of about 6 mm to about 12 mm.

The pre-formed unit of the chewy composition can have a diameter ofabout 6 mm to about 12 mm and a thickness of about 0.5 mm to 8 mm.

The second composition can be a pre-formed unit of a lipidic compositionthat can comprise one or more lipidic materials and one or more bulkingagents.

The one or more lipidic materials can be selected from the groupconsisting of vegetable fats, nut fats, seed fats, and combinationsthereof.

The one or more lipidic materials can comprise cocoa fat.

The pre-formed unit of the lipidic composition can comprise about 10% toabout 60% w/w of the one or more lipid materials and about 10% to about60% w/w of the one or more bulking agents.

The active ingredient can be present in the pre-formed unit of thelipidic composition.

The pre-formed unit of the lipidic composition can be stable such that,after being stored for a time of 28 days at a temperature of 50° C. anda relative humidity of 60%, the pre-formed unit of the lipidiccomposition comprises less than about 2% by weight of active ingredientdegradation products relative to the weight of the active ingredient.

The pre-formed unit of the lipidic composition can have a diameter ofabout 0.5 mm to about 10 mm.

The multicomponent composition can include an outer layer surroundingthe first component and the second component.

The second composition can be a particulate material. The particulatematerial specifically can be in the form of a powder, granules, beads,or the like.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a cross-section of a multicomponent composition according toan exemplary embodiment of the present disclosure illustrating a gummycomposition completely surrounding a second composition in a shell/coreconfiguration;

FIG. 2 is a cross-section of a multicomponent composition according toan exemplary embodiment of the present disclosure illustrating a gummycomposition partially surrounding a second composition;

FIG. 3 is a cross-section of a multicomponent composition according toan exemplary embodiment of the present disclosure illustrating a gummycomposition and a second composition substantially in a side-by-sideconfiguration;

FIG. 4 is a cross-section of a multicomponent composition according toan exemplary embodiment of the present disclosure illustrating aplurality of second compositions configured interior to a gummycomposition;

FIG. 5 is a cross-section of a multicomponent composition according toan exemplary embodiment of the present disclosure illustrating a firstgummy composition surrounding a second gummy composition;

FIG. 6 is a cross-section of a multicomponent composition according toan exemplary embodiment of the present disclosure illustrating an outergummy composition and an inner composition with a first interveninglayer and a second intervening layer;

FIG. 7 is a cross-section of a multicomponent composition according toan exemplary embodiment of the present disclosure illustrating a secondcomposition between two gummy compositions

FIG. 8 is a cross-section of a multicomponent composition according toan exemplary embodiment of the present disclosure illustrating a gummycomposition and a second composition that is partially blended into thegummy composition;

FIG. 9 is a cross-section of a multicomponent composition according toan exemplary embodiment of the present disclosure illustrating a gummycomposition surrounding a second composition that is separated from thegummy composition with a barrier layer;

FIG. 10 is a graph showing the percent weight change (moisture uptake)of exemplary tabletted compositions according to the present disclosurewhen subject to storage for 14 days at 40° C. and 75% relative humidity;and

FIG. 11 is a graph showing the change in weight of exemplary tablettedcompositions according to the present disclosure when subject to storagefor 7 days at 40° C. and 75% relative humidity; and

FIG. 12 is a graph showing the change in weight of exemplary chewycompositions according to the present disclosure when subject to storagefor 5 days at 40° C. and 75% relative humidity.

DETAILED DESCRIPTION OF THE DISCLOSURE

The invention now will be described more fully hereinafter throughreference to various embodiments. These embodiments are provided so thatthis disclosure will be thorough and complete, and will fully convey thescope of the invention to those skilled in the art. Indeed, theinvention may be embodied in many different forms and should not beconstrued as limited to the embodiments set forth herein; rather, theseembodiments are provided so that this disclosure will satisfy applicablelegal requirements. As used in the specification, and in the appendedclaims, the singular forms “a”, “an”, “the”, include plural referentsunless the context clearly dictates otherwise.

The present disclosure relates to oral, multicomponent dosage forms thatare suitable for delivery of active ingredients in a manner that ishighly palatable and that thusly improves compliance with dosingrequirements for the active ingredients. In one or more embodiments, thedosage forms can comprise a gummy composition as at least one of thecomponents. The gummy composition may completely or at least partiallysurround one or more different compositions that are also included inthe multicomponent dosage form. While two or more different gummycompositions may be used, in some embodiments, multicomponent dosageforms of the present disclosure can comprise at least one gummycomposition and at least one different composition that is also in adifferent form. Such different composition can be referred to as asecond composition (the gummy composition being a first composition).The multicomponent compositions thus may comprise at least two, at leastthree, at least four, or even more different compositions. The activeingredient can be included in the gummy composition, in the one or moredifferent composition, or in the gummy composition and one or more ofthe different composition(s).

A “gummy” as used herein is understood to refer to a confectionary thatcan be defined by its compositional nature, as otherwise describedherein, and also by its chewy texture and mouthfeel. Gummy bears, gummyworms, and other gummy candies are known in the art, and a person ofordinary skill in the art would understand the term “gummy” to refer toa composition having such texture and mouthfeel.

An “active ingredient” as used herein can include any compound,composition, or like material that may be included in a dosage form fordelivery to an individual to achieve any one or more of a desirednutritional purpose, medicinal purpose, and therapeutic purpose. In someembodiments, an active ingredient can be an API. Non-limiting examplesof APIs include non-steroidal anti-inflammatory drugs (NSAIDs—e.g.,ibuprofen, diclofenac, and naproxen), analgesics (e.g., acetaminophen,aspirin), antihistamines, decongestants, antitussives, expectorants,sleep aids, antibiotics, laxatives, anti-diarrheals, anthelmintics, andantacids. Further, non-limiting examples of materials that may beincluded as an active ingredient include vitamins, minerals,phytonutrients (e.g., carotenoids, flavonoids, resveratrol, andglucosinolates), fiber, fatty acids, amino acids, polypeptides, andbotanicals. An active ingredient can include any plant-derived materialthat is safe for human consumption, including herbal extracts, botanicalextracts, and the like. Other materials, such as prebiotics, probiotics,can also be used as an active ingredient. In some embodiments, an activeagent according to the present disclosure may be classified as dietarysupplement according to the Dietary Supplement Health and Education Actof 1994, whereby a dietary supplement is defined to mean a product(other than tobacco) intended to supplement the diet that bears orcontains one or more of the following dietary ingredients: a vitamin, amineral, an herb or other botanical, an amino acid, a dietary substancefor use by man to supplement the diet by increasing the total dietaryintake, or a concentrate, metabolite, constituent, extract, orcombination of any of the aforementioned ingredients.

The multicomponent dosage forms can be configured with the differentcompositions combined in a variety of conformations. In someembodiments, the gummy composition may partially or completely surroundthe second composition. For example, FIG. 1 illustrates a multicomponentcomposition 10 wherein a gummy composition 12 completely surrounds asecond composition 14, thus forming a shell/core configuration. FIG. 2illustrates, as a further example, a multicomponent composition 20wherein a gummy composition 22 partially surrounds a second composition24, and FIG. 3, for example, illustrates a multicomponent composition 30wherein a gummy composition 32 and a second composition 34 aresubstantially in a side-by-side configuration. As a further example,FIG. 4 illustrates a multicomponent composition 40 wherein a pluralityof second compositions 44 are configured interior to a gummy composition42. The plurality of second compositions 44 may be separate units formedof the same composition or may be separate units formed from two or moredifferent compositions (e.g., units 44 a and 44 b being formed ofdifferent compositions). The second compositions 44 illustrated in FIG.4 may be, for example, minitabs as further described herein. In theillustrated embodiments, it is understood that one or more active agentsmay be included in the gummy composition, the second composition, orboth. In a further example shown in FIG. 5, a first gummy composition 52a can surround a second gummy composition 52 b. In such embodiments, oneor more active agents may be included in one or both of thecompositions. As before, the first gummy composition can completely orpartially surround the second gummy composition, or the gummycompositions may be in a side-by-side arrangement. In some embodiments,the multicomponent dosage form can comprise a plurality of layers. Asillustrated in FIG. 6, the multicomponent composition 60 can comprise anouter gummy composition 62 and an inner composition 64 with a firstintervening layer 63 and a second intervening layer 65. The layers canhave different compositions and can be of different thicknesses. Activeagents may be provided in any or all of the gummy composition, the innercomposition 64, the first intervening layer 63, and the secondintervening layer 65. It is understood that the nature of such dosageforms is not limited by the naming, and each of elements 62, 63, 64, and65 may be considered layers. In some embodiments, a stackedconfiguration may be utilized. For example, as seen in FIG. 7, themulticomponent composition 70 can comprise a second composition 74between two gummy compositions 72 a and 72 b. It is understood that thereverse situation is also encompassed wherein a gummy composition may beprovided between two different compositions (i.e., between two layers ofthe second composition or between a layer of the second composition anda layer of a third composition).

In one or more embodiments, a dosage form as described herein can beadapted to compartmentalize the active ingredient into a portion of theoverall dosage form that is separate from the gummy composition. Acompartmentalized gummy dosage form can afford stability for the activeingredient(s) and can permit consistent release of the actives from thegummy dosage form while also providing optimal organoleptic response toaid user acceptance and compliance. Compartmentalization is furtherbeneficial for any one or more of the following: the active ingredientsare not subject to the same thermal stress that is imparted on the gummybase during the cooking and depositing process; the active ingredientsare physically separated from the gummy base to limit the potential forchemical and physical interactions during the manufacture and followinglong-term storage; the active ingredients can be controlled to a highquality limit in respect of dose, dose uniformity, and degradation limitcompared to the gummy base; and the active ingredients are subject to nooverage inclusion or only limited overage inclusion to take account ofgross losses during manufacture. While it is thus evident thatcompartmentalization can be beneficial, in one or more embodiments,active ingredients can be included in a gummy composition, particularlyif the above considerations are not critical to the overall nature ofthe dosage form. Likewise, active ingredients may be present in both thegummy composition as well as one or more further compositions includedin the multicomponent dosage form.

Where compartmentalization is desirable, the multicomponent dosage formsof the present disclosure can be particularly useful. For example, acompartmentalized gummy dosage form can be configured such that theactive ingredient is partially or completely present within a secondcomposition that is provided in combination with the gummy composition.As already noted above, the second composition may be in the form of oneor more solid or semi-solid cores that are embedded within the gummycomposition so as to be partially or completely surrounded by the gummycomposition, the second composition may be in the form of a layerpresent within the multicomponent dosage form, and/or the secondcomposition may be substantially attached, adhered, or otherwiseinterconnected with the gummy composition (e.g., the side-by-sidearrangement). Separating the active ingredient from the gummy base viacompartmentalization in the second composition allows the activeingredient (within the second composition) to be incorporated into thegummy dosage form during a downstream processing step and not theupstream cooking step, which carries the highest thermal stress. Inaddition, by separating the compounding step for the second compositionfrom the manufacturing process for the gummy composition (particularlyone or more deposition steps), the control of the key quality attributesfor the active ingredient is not limited by the inflexible andstress-bound process for forming the gummy composition.

Although compartmentalization can be advantageous, it is not required.In some embodiments, the different compositions forming themulticomponent dosage forms can be partially blended or otherwisecombined so that the second composition is not necessarily in the formof a discrete “unit” within the gummy composition. As a non-limitingexample, as seen in FIG. 8, the multicomponent composition 80 cancomprise a gummy composition 82 and a second composition 84 that ispartially blended into the gummy composition. As illustrated, the secondcomposition 84 has a main body 84 a and a tail 84 b that substantiallyblends into the gummy composition. Such conformation may be referred toas a “swirl”, and other like structures are also encompassed by thepresent disclosure.

The nature of the second composition can be particularly relevant inproviding the significant advantages over conventional gummy matrixformulations. In particular, the second composition can be provided withspecific properties that confer consistent release of the activeingredient and maximize the organoleptic response of the overall gummydosage form.

In the multicomponent dosage forms of the present disclosure, the gummycomposition, in some embodiments, can be configured according to knownrecipes. For example, it is generally known to prepare a gummycomposition by combining gellants, sweeteners, water, colors, andflavors. The combined materials can be heated to form a thickenedslurry, which can then be poured into molds to provide the desiredshape. The molds may be coated with a release agent or formed from amaterial designed to facilitate release. The formed gummy compositionsare allowed to cool and set to the final, desired shape when releasedfrom the molds. If desired, one or more coating layers can be applied tothe formed gummy composition.

In one or more embodiments, a gummy composition utilized according tothe present disclosure can be a hydrocolloid system. In particular, ahydrocolloid system can comprise one or more hydrophilic long-chainpolymers, one or more hydrophilic bulking agents, and a water source.Optionally, the hydrocolloid system can include one or more furtheringredients, such as pH modifiers, coloring agents, and/or flavoringagents. The outer composition particularly can be substantially a gummybase. The outer composition may particularly be characterized as beingan elastic or viscoelastic material.

Hydrophilic, long-chain polymers useful in a hydrocolloid systemaccording to the present disclosure include long chain carbohydrates(e.g., polysaccharides) as well as various proteins. The hydrophilic,long-chain polymer preferably is configured to thicken and form a gelupon hydration (with or without heating). Non-limiting examples ofhydrophilic, long-chain polymers that may be included in a hydrocolloidsystem for use as a gummy composition according to the presentdisclosure include: gelatin, pectin, carrageenan, gellan gum, locustbean gum, gum arabic, xanthan gum, starch, methylcellulose, agar,konjac, alginates, and combinations thereof (including single, binary,tertiary, or quaternary blends).

Hydrophilic bulking agent useful in a hydrocolloid system according tothe present disclosure include saccharides or saccharide derivatives asotherwise described herein. In exemplary embodiments, hydrophilicbulking agents can include oligofructose, dextrins, monosaccharides(e.g., fructose or glucose), disaccharides (e.g., palatinose orsucrose), hydrogenated carbohydrates, also known as sugar alcohols(e.g., polyols, monosaccharide alcohols, disaccharide alcohols, oroligosaccharide alcohols), and syrups (e.g., glucose syrup or fructosesyrup). The hydrophilic bulking agent further may be a syntheticmaterial, such as soluble fibers (e.g., polydextrose).

The hydrating materials used in the hydrocolloid system can include anyvariety of materials configured to donate water to the hydrophilic,long-chain polymer. The hydrating material particularly can besubstantially pure water; however, the hydrating material may be anaqueous composition including one or more additives, such as a syrup, afruit juice, or a flavoring liquid.

In some embodiments, a pH modifier particularly can be an acidifier.Non-limiting examples of acidic materials that may be used includecitric acid, malic acid, lactic acid, tartaric acid, fumaric acid,phosphoric acid, ascorbic acid, sodium bisulphate, and combinationsthereof.

The relative amount of the components utilized in a gummy compositioncan vary. The following embodiments exemplify the relative amounts ofthe components that may be utilized. All percentages are on aweight/weight basis (the weight of the specific component relative tothe total weight of the gummy composition).

The gummy composition can comprise about 70% to about 94%, about 75% toabout 90%, or about 78% to about 86% w/w of the hydrophilic bulkingagent(s), particularly one or more saccharides or saccharidederivatives. Within the above ranges, the hydrophilic bulking agent(s)can comprise: about 1% to about 30%/a, about 5% to about 20%, or about8% to about 18% w/w of one or more hydrogenated carbohydrates; about100/% to about 70%, about 15% to about 65%, or about 20% to about 60%w/w of sugar syrup solids; about 10% to about 70%, about 15% to about65%, or about 20% to about 60% w/w of granular sugar.

The gummy composition can comprise about 1% to about 20%/a, about 1% toabout 15%, or about 2% to about 7% w/w of the one or more hydrophilic,long-chain polymers.

The gummy composition can comprise about 5% to about 35%, about 10% toabout 25%, or about 16% to about 22% w/w of water.

The gummy composition can comprise up to about 2%, up to about 1.5%, orup to about 1% w/w of a pH modifier. More particularly, about 0.1% toabout 1%, about 0.2% to about 0.8%, or about 0.3% to about 0.6% w/w ofthe pH modifier can be used.

The gummy composition can comprise up to about 4%, up to about 2%, or upto about 1% of coloring agents.

The gummy composition can comprise up to about 4%, up to about 2%, or upto about 1% of flavoring agents.

In a non-limiting example, a gummy composition can comprise about 1% toabout 4% by weight of pectin; 0% to about 3% by weight of furtherhydrophilic, long-chain polymers (e.g., starch, gelatin, carrageenan,cellulosic material, agar, or gelan); about 10% to about 70% by weightsugar syrup solids (e.g., glucose syrup solids); about 10% to about 70%by weight granular sugar (e.g., sucrose); about 0% to about 30% byweight of hydrogenated carbohydrates (e.g., sorbitol syrup, glycerol,mannitol, maltitol, erythritol, isomalt); about 0.1% to about 1.5% byweight citric acid (or other pH modifier); and the balance water, withweights being based on the total weight of the gummy composition.

The nature of the gummy composition used in forming the multicomponentdosage forms discussed herein can cause the dosage forms to besubstantially chewable. A “chewable” dosage form, while capable of beingswallowed whole, is configured specifically for chewing prior toswallowing. As such, a chewable dosage form is specificallydistinguishable from a non-chewable dosage form, such as a vitamintablet or capsule that is intended to be swallowed whole. In someembodiments, the term chewable can thus mean that the dosage form isintended to be retained in the mouth of the consumer for a period oftime prior to swallowing during which time the dosage form may undergo achange in structure that facilitates ease of swallowing. The chewabledosage form may thus be reduced to smaller pieces through mastication.In some embodiments, the chewable dosage form may be configured to atleast partially dissolve within the mouth of the consumer. As such, thechewable dosage form may also be dissolvable and may thus be referred toas a “melt-away” form.

The second composition used in the multicomponent dosage forms of thepresent disclosure can be provided in a variety of forms andcombinations of materials. As such, the multicomponent dosage form canbe configured as needed to achieve not only the desired delivery of oneor more active ingredients but also to provide one or more desiredorganoleptic properties. For example, the second composition may be in aform such that it has a texture that is substantially different from thetexture of the gummy composition or a form such that it has a texturethat is substantially the same as the texture of the gummy composition.In one or more embodiments, the second composition (or one or morefurther compositions) may be provided in one or more of the followingforms: crunchy or otherwise brittle; powdery; resilient; or chewy.Similarly, the second composition (or one or more further compositions)can have a taste that is complimentary or contrasting to the gummycomposition. For example, where the gummy composition is typicallysweet, the second composition may be substantially sour. A variety offlavor and taste combinations can be prepared in light of the presentdisclosure.

The second composition preferably is in the form of a solid material.The solid form is particularly maintained not only at standard roomtemperatures but also at elevated temperatures, such as up to about 100°C. in some embodiments. As such, the second composition specifically maynot be in the form of a viscous fluid at such elevated temperatures.

In one or more embodiments, the second composition can be in the form ofa particulate material. The term “particulate material” is intended tomean any material that is in the form of a plurality of individualparticles of a typically small size, such as having an average size ofabout 0.5 mm or less, about 0.25 mm or less, or about 0.1 mm or less.Average particle size particularly can be in the range of about 0.1 μmto about 0.5 mm, about 0.5 μam to about 0.25 mm, or about 1 μam to about0.1 mm. A particulate material can be in the form of a powder. Aparticulate material further encompasses granules, beads, pearls,prills, and other like forms.

In one or more further embodiments, the second composition canspecifically be in a unit form, and the individual unit(s) may bepre-formed prior to combination with the gummy composition. Suchpre-formed unit structure can be particularly useful to achievecompartmentalization of an active ingredient but can also be useful forease of manufacturing of the multicomponent dosage forms. The secondcomponent thus may comprise a single, pre-formed solid unit or aplurality of pre-formed solid units. The unit or units can be in theform of any generally recognized oral dosage form, such aspharmaceutical dosage forms that are intended for oral administration.Non-limiting examples of solid dosage forms that are encompassed by thepresent disclosure include tablets, caplets, hard shell capsules, softshell capsules, microcapsules, and pastilles. Any other solid formssuitable for oral administration are likewise encompassed. Thepre-formed unit dosage form unit may be substantially homogeneous incomposition throughout the unit. The pre-formed dosage form unit mayinclude a coating (e.g., a coated tablet). The solid dosage form unitmay be hollow (e.g., a gelatin capsule defining a hollow interior), andthe hollow interior of the solid dosage form may be empty or may includeone or more additives. The additive, for example, may be an activeingredient, may be a flavor, and/or may be a material designed toprovide a specific sensation or organoleptic effect. Materialspositioned within a hollow interior of a solid dosage unit can be in theform of a liquid, a solid unit, solid particles (including powders andbeads), and/or microcapsules. A hollow, solid dosage unit may, forexample, include a material that is intended to remain separated fromanother material in the multicomponent dosage form until administration.For example, the hollow, solid dosage unit may include a flavor that isintended to complement another flavor present in the multicomponentdosage form. Likewise, hollow, the solid dosage unit may include amaterial that is configured to react with another material in themulticomponent dosage form (which other material may likewise beincluded in a hollow, solid dosage unit). For example, an acidicmaterial and a basic material may be included in the multicomponentdosage form, and one or both of the materials may be included in ahollow, solid dosage unit so that, upon chewing by a user, the twomaterials are combined to provide an effervescing effect. While thesecond component can include a liquid, the liquid preferably iscontained within a solid unit (e.g., a shell or capsule) so that thesolid unit effective separates the liquid from the outer gummycomposition of the multicomponent dosage form.

The second composition is thus defined in some embodiments in relationto being a pre-formed unit. This allows for preparation of a widevariety of compositions that can include a great number of differentmaterials to allow for the greatest variation in composition taste andorganoleptic nature. As described in greater detail below, thepre-formed solid dosage units can be prepared in advance and stored fora desired length of time prior to combining the pre-formed solid unitswith the gummy composition to provide the final multicomponent dosageform.

The second composition specifically can be in a compressed form and thusbe a compressed solid. The second composition preferably is solid atstandard temperature and has a melting temperature of no lower than 40°C., no lower than 45° C., or no lower than 50° C. The compressed solidcan be formed from a plurality of particles that can vary in size fromfine powders to coarse beads or pellets. A compressed solid thus may becompacted to provide its final shape. The compressed solids may beprepared from a variety of materials and may take on a variety ofconfigurations. While specific materials are further described herein,in one or more embodiments, compressed solids according to the presentdisclosure can comprise one or more saccharides, saccharide derivatives,lipids, cellulosic polymers, cellulosic polymer derivatives, and/orinorganic salts as major components thereof. It is understood, however,that specific compositions will comprise additional components.

In some embodiments, the second composition can be substantially in theform of a tablet, caplet, or the like. Although the term “tablet” isused, it is understood that the tablet can have a variety of shapes,such as being substantially spherical, cubed, or the like. In preferredembodiments, the tablets can be in the form of a compressed matrixcomprising a mixture of materials.

In some embodiments, a second composition in a substantially tablettedform can comprise a compressible material of a nature and in an amountsuitable to form a compressed matrix of desired hardness. For example,the tabletted composition can be compressed to a hardness of about 2 Kpto about 35 Kp. In some embodiments, the tabletted composition may be ina rapidly disintegrating form (i.e., under mouth conditions). In suchembodiments, the tabletted composition may be compressed to a hardnessof about 2 Kp to about 20 Kp, about 4 Kp to about 20 Kp, about 4 Kp toabout 12 Kp, or about 4 Kp to about 8 Kp. In further embodiments, it maybe desirable to provide a core with increased hardness that exhibitsslower disintegration in the mouth of an individual. As such, the coremay be compressed to a hardness of about 6 Kp to about 35 Kp, about 8 Kpto about 25 Kp, or about 10 Kp to about 20 Kp. The hardness may be asmeasured prior to combination with the gummy composition. Accordingly,the tablets can be formed to have a first hardness as defined above andbe configured to reduce in hardness upon combination with the gummycomposition, for example, in response to ingress of moisture from thegummy composition. If desired, the tablets can be configured to have afirst hardness that facilitates ease of manufacturing and be configuredto reduce in hardness after combination with the gummy composition suchthat chewing of the gummy composition causes the tablet to substantiallydisintegrate as opposed to requiring fracturing during chewing. Suchcharacteristics can be modified as desired.

Discussion herein of “mouth conditions” can relate to one or morecharacteristics (in any combination) associated with the presence of anitem in the mouth of an individual. For example, mouth conditions caninclude any combination of temperature, moisture, and pH typically foundin the mouth of a human as well as the shear, compression, and othermechanical forces that may be applied by the teeth during chewing. Mouthconditions particularly can relate to being in contact with saliva. Insome embodiment, mouth conditions can particularly mean contact withsaliva at the temperature and pH typically present in the human mouth.

The tablet composition can comprise as a major component a carriermaterial. The carrier material may particularly be a compressiblematerial, and a single carrier material or a plurality of differentcarrier materials can be used. For example, in some embodiments, acarrier material can be selected from the group consisting ofsaccharides, saccharide derivatives, inorganic salts, and combinationsthereof. Beneficially, such materials may also be compressible so as tobe useful in forming a compressed structure, as further describedherein. A carrier may also be characterized as a bulking agent, andexamples of materials below for use as a carrier may also be used in oneor more embodiments as a bulking agent.

A tablet in some embodiments may be compressed to form a solid monolith.In some embodiments, a monolithic structure need not necessarily becompressed but may be prepared by any method wherein a substantiallycontinuous structure is formed.

The term “saccharide” as used herein (including in relation to allcompositions described herein) can encompass sugar, starch, andcellulose materials. A saccharide can be a monosaccharide, adisaccharide, an oligosaccharide, or a polysaccharide. Exemplarymonosaccharides include glucose, fructose, and galactose. Exemplarydisaccharides include sucrose, lactose, lactulose, maltose, trehalose,cellobiose, and chitobiose. Exemplary oligosaccharides includefructo-oligosaccharides, galactooligosaccharides, and mannanoligosaccharides. Exemplary polysaccharides include glucans, starches,celluloses, pectins, xylans, arabinoxylans, mannans, and galactomannans.Saccharide derivatives can include any material that is derived from asaccharide. In particular, saccharide derivatives may be formed bysubstitution of one or more hydroxyl groups on the compound to form, forexample, amino sugars, acidic sugars, deoxy sugars, sugar alcohols,glycosylamines, and sugar phosphates. Non-limiting examples of sugaralcohols include erythritol, xylitol, ribitol, mannitol, sorbitol,volemitol, isomalt, maltitol, and lactitol. Saccharide derivatives canalso encompass artificial sweeteners, such as sucralose.

In some embodiments, carrier materials can include one or more of thefollowing: sucrose, fructose, lactose, maltose, mannitol, xylitol,maltitol, sorbitol, hydrogenated starch hydrosylate, maltodextrin,cellulose, microcrystalline cellulose, hydroxypropyl cellulose,hydroxypropylmethyl cellulose, hydroxyethyl cellulose, starch,pre-gelatinized starch, dicalcium phosphate, guar gum,carboxymethylcellulose (and salts thereof—e.g., sodium salts),polyethylene oxide, polyethylene glycol (and co-polymers thereof—e.g.,poloxamer/PLURONIC®).

Disintegrants are understood in the art to be materials that facilitatethe de-aggregation of a compressed dosage form under desired conditions,such as in one or more areas along the gastrointestinal tract, which canbe effective to facilitate release of an active agent at one or moredesired locations. Any material recognized as a disintegrant may be usedin the present core compositions. Non-limiting examples of disintegrantsthat may be used include croscarmellose sodium, crospovidone (i.e.,crosslinked polyvinyl pyrrolidone), polyvinyl acetate, silica, andsodium starch glycolate.

A tablet composition according to the present disclosure can alsoinclude further components. For example, various processing aids may beincluded. Non-limiting examples of processing aids include magnesiumstearate, stearic acid, glyceryl monostearate, sodium stearyl fumerate,talc, silicon dioxide, polyvinylpyrrolidone (povidone), polyvinylalcohol, and hydroxypropylmethyl cellulose. Processing aids may be anymaterial recognized in the art as a lubricant in a tableting process, asa glidants to aid powder flow, or a binder to aid powder granulation.

A tablet composition further may include one or more agents adapted tomodify, particularly improve, the organoleptic properties of the tabletcomposition. For example taste-making agents may be utilized.Non-limiting examples of taste-masking agents include cyclodextrins andion exchange resins. Further, flavoring agents may be utilized.Non-limiting examples of flavoring agents include citric acid, tartaricacid, confectionary sugars, artificial sweeteners (e.g., acesulfamepotassium, aspartame, neotame, saccharine, and sucralose), salts (e.g.,sodium chloride), plant extracts (e.g., vanilla, luo han guo), andessential oils.

The second composition, according to one or more embodiments, may becharacterized as being an orally disintegrating tablet (ODT), a fastmelt or quick melt dosage form, or an orodispersible dosage form. Insome embodiments, the tablet can be in a rapidly disintegrating form. Asused herein, rapid disintegration can be defined as achievingsubstantially complete disintegration under mouth conditions in a timeof less than 20 seconds, less than 15 seconds, or less than 10 seconds.This can be calculated as the time from which the tablet becomes exposedto the mouth conditions. For example, when the tablet is completelysurrounded by an outer gummy composition, the time to disintegration canbe calculated from time when the tablet becomes exposed through at leastpartial removal of the outer gummy composition, such as through chewingand/or dissolving of the gummy composition. Substantially completedisintegration can mean de-aggregation, dispersion, or dissolution ofthe core to an extent that no portion of the core remains as a solidmonolith compact having a size that is greater than 50%, greater than10%, greater than 5%, or greater than 2% of the size of the originalcore.

A rapidly disintegrating tablet composition in some embodiments may havean initial size wherein a maximum dimension thereof is about 6 mm toabout 12 mm. In some embodiments, the rapidly disintegrating tabletcomposition may be defined by a diameter and a thickness. For example,the rapidly disintegrating tablet composition can have a diameter ofabout 6 mm to about 12 mm, about 7 mm to about 12 mm, or about 8 mm toabout 12 mm, and the rapidly disintegrating tablet composition can havea thickness of about 0.5 mm to about 8 mm, about 1 mm to about 6 mm, orabout 2 mm to about 6 mm.

When the multicomponent dosage form is substantially in a core/shellconfiguration (e.g., wherein the outer gummy composition is completelysurrounding one or more cores, the overall dosage form can have amaximum outer dimension of about 10 mm to about 35 mm. In someembodiments, the dosage form can have a diameter, length, or width ofabout 10 mm to about 35 mm, about 12 mm to about 32 mm, or about 15 mmto about 30 mm, and the dosage form can have a thickness of about 10 mmto about 30 mm, about 10 mm to about 25 mm, or about 10 mm to about 20mm.

In one or more embodiments, the dimensions of a core composition withina gummy composition can vary relative to the dimensions of the gummycomposition. In particular, it has been found that overall productcharacteristics can be improved by maintaining a minimum “shell”thickness. Specifically, it can be desirable for the thickness of thegummy composition shell (measured as the distance from the outer surfaceof the core composition to the outer surface of the gummy composition)to be about 1.5 mm or greater, about 2 mm or greater, or about 2.5 mm orgreater, such as about to about 1.5 mm to about 10 mm or about 2 mm toabout 8 mm. Such thickness specifically can apply to all points of theshell surrounding the core composition. The gummy shell thickness neednot necessarily be constant at all points so long as the minimum shellthickness is met at all point of the gummy shell.

When a core/shell configuration is used, the multicomponent dosage formcan include only a single core. In some embodiments, though, a pluralityof cores, each of the same composition or of different compositions, maybe included. For example, in some embodiments, the multicomponent dosageform can comprise an outer gummy composition shell surrounding a singlecore formed of the second composition (e.g., in a tablet form or in adifferent form as otherwise described herein). In other embodiments, themulticomponent dosage form can comprise an outer gummy compositionsurrounding two or more cores, which cores may all be formed of the samecomposition or may be formed of two or more different compositions. Whena plurality of cores is used, less than all of the cores may be rapidlydisintegrating. Moreover, the plurality of cores may have differentsizes. Regardless of core number and dimensions, it is preferably forthe minimum gummy shell thickness as discussed above to be maintained atall points in the gummy shell.

Shapes and sizes of the tablet composition as provided above areunderstood to be exemplary in nature and not limiting of the presentdisclosure. In some embodiments, for example, a unit formed acomposition that is different from the gummy composition may be in asubstantially non-tableted form. Exemplary embodiments of non-tabletunit forms include wafers and films. Moreover, the units formed of thesecond composition may be freeze-dried and may be present as a singlemass or as particulates. In some embodiments, nanoparticles and/ormicroparticles may be used. Microparticles can have an average diameterof about 1 micron to about 1,000 microns, about 5 microns to about 750microns, or about 10 microns to about 500 microns. Nanoparticles canhave an average diameter of about 5 nm to about 1,000 nm, about 10 nm toabout 900 nm, or about 50 nm to about 750 nm.

The relative amount of the components utilized in forming a rapidlydisintegrating composition can vary. The following embodiments exemplifythe relative amounts of the components that may be utilized. Allpercentages are on a weight/weight basis (the weight of the specificcomponent relative to the total weight of the composition).

A rapidly disintegrating tablet composition (or other form forcombination with a gummy composition to form the multicomponent dosageform) can comprise about 5% to about 80%, about 25% to about 80%, orabout 40% to about 80% w/w of a carrier material, which particularly canbe a compressible material, including one or more saccharides orsaccharide derivatives and/or one or more inorganic salts. In someembodiments, a rapidly disintegrating tablet composition can comprisegreater than 50%, greater than 55%, or greater than 60% w/w of thecarrier material or materials.

A rapidly disintegrating tablet composition can comprise about 0.1% toabout 15%, about 1% to about 10%, or about 3% to about 8% w/w of adisintegrant.

A rapidly disintegrating tablet composition can comprise about 0.1% toabout 60%, about 1% to about 55%, or about 5% to about 50% w/w of activeingredient(s).

A rapidly disintegrating tablet composition can comprise about 0.1% toabout 10%, about 0.2% to about 5%, or about 0.5% to about 3% w/w of oneor more processing aids.

A rapidly disintegrating tablet composition can comprise up to about 4%,up to about 2%, or up to about 1% w/w of flavoring agents and/or tastemasking agents (e.g., about 0.01% to about 4%, about 0.05% to about 2%,or about 0.1% to about 1% w/w).

In some embodiments, one or more of the materials used in forming arapidly disintegrating tablet composition can be hydrophilic. Forexample, a hydrophilic carrier material can be used, particularly acarrier material that allows for the light compressibility needed toform the tablet. The use of a hydrophilic carrier can improve tabletstability since the hydrophilic carrier may permit rapid water ingressbut have a low equilibrium water content such that the amount of waterthat is absorbed into the tablet reaches a plateau without causingdeliquescence of the tablet.

In some embodiments, a composition to be combined with a gummycomposition to provide a multicomponent dosage form may be characterizedas being in the form of mini-tablets (“minitabs”). A minitab may, insome embodiments, be considered to be in a rapidly disintegrating form.Alternatively, a minitab may be disintegrating but may undergo suchprocess as a slower rate than otherwise described above. As such, aminitab may have a greater hardness than a rapidly disintegratingtablet. Whereas hydrophilic excipients may be useful in a rapidlydisintegrating tablet, a minitab may benefit from the use of hydrophobicexcipients. In particular, hydrophobic excipients can function to reducethe potential for water ingress and additionally have a low equilibriumwater content such that the amount of water that is absorbed into theminitab reaches a plateau without causing stability issues within theminitab. If desired, however, hydrophilic excipients may likewise beused in a minitab.

A minitab can be fracturable and thus can be characterized in relationto a brittleness index of the core, typically in the range of 0.05 to1.0. The brittleness index value may be as measured before combinationwith the gummy composition, as it is understood that, in someembodiments, the brittleness index may change after combination with thegummy composition. Preferably, the brittleness index value prior tocombination with the gummy composition can be about 0.1 to about 0.99,about 0.2 to about 0.98, about 0.25 to about 0.97, or about 0.5 to about0.95.

A minitab may have an initial size wherein a maximum dimension thereofis about 2 mm to about 10 mm. In some embodiments, a minitab compositionmay be defined by a diameter and a thickness. For example, the minitabcomposition can have a diameter of about 2 mm to about 10 mm, about 2 mmto about 6 mm, or about 3 mm to about 4 mm, and the minitab compositioncan have a thickness of about 0.5 mm to about 6 mm, about 1 mm to about5 mm, or about 3 mm to about 4 mm. A multicomponent dosage formincluding one or more minitab compositions can have overall dimensionsas already noted above.

The number and nature of minitabs utilized in an oral, chewable dosageform can be substantially as otherwise described above. In embodimentswherein a minitab composition is utilized, it can be beneficial toinclude a plurality of cores. For example, an oral, chewable dosage formof the present disclosure can include 2 to 20, 2 to 15, or 2 to 10minitabs surrounded by an outer gummy composition. Each of the pluralityof minitabs can have the same size or can be of different sizes and/orof different composition.

The use of the term “minitab” is meant to be descriptive and notnecessarily limiting of the shape thereof. As already described above, aminitab can be substantially in the shape of a tablet, a sphere (orbead), spheroid, cube, wafer, film, or other like shape.

The relative amount of the components utilized in forming a minitabcomposition can vary. The following embodiments exemplify the relativeamounts of the components that may be utilized. All percentages are on aweight/weight basis (the weight of the specific component relative tothe total weight of the minitab composition).

A minitab composition can comprise about 15% to about 90%, about 25% toabout 90%, or about 50% to about 90% w/w of a carrier material. In someembodiments, the carrier material may be a compressible material and mayalso include a hydrophilic diluent. The total amount of the carriermaterial may be selected from the group of saccharides or saccharidederivatives and/or inorganic salts. In some embodiments, a minitabcomposition can comprise greater than 50%, greater than 55%, or greaterthan 60% w/w of the carrier material or materials. In furtherembodiments, a minitab composition can comprise about 5% to about 80% orabout 40% to about 80% w/w of a compressible material and can compriseabout 10% to about 60% or about 20% to about 50% w/w of a hydrophilicdiluent.

A minitab composition can comprise about 0.1% to about 15%, about 1% toabout 10%, or about 3% to about 8% w/w of a disintegrant.

A minitab composition can comprise about 0.1% to about 60%, about 1% toabout 55%, or about 5% to about 50% w/w of active ingredient(s).

A minitab composition can comprise about 0.1% to about 10%, about 0.2%to about 5%, or about 0.5% to about 3% w/w of one or more processingaids.

A minitab composition can comprise up to about 4%, up to about 2%, or upto about 1% w/w of flavoring agents and/or taste masking agents (e.g.,about 0.01% to about 4%, about 0.05% to about 2%, or about 0.1% to about1% w/w).

In one or more embodiments, the second composition can be in a formexhibiting specific textural properties. For example, the secondcomposition can be provided in a pre-formed unit that exhibits chewinessor has a chewy texture. As would be understood in the art, a unit formhaving such texture would require repeated chewing within the mouth of aconsumer in order to reduce the unit to pieces suitable for ease ofswallowing. This is distinguishable from a unit that dissolves or isreduced substantially to a power or particulate form with little or nochewing. A chewy texture can be substantially matched to the texture ofthe gummy composition or may exhibit differing qualities. Embodiments ofmulticomponent dosage forms including a second composition substantiallyin the form of a chew can likewise be compressed solids and can beconfigured as otherwise described herein (e.g., core/shell;side-by-side; partially surrounded; etc.).

In one or more embodiments, a second composition substantially in theform of a chew can comprise one or more carriers, one or morehydrophilic polymers, and optionally one or more active ingredients. Insome embodiments, one or more disintegrants may be included to providethe chewiness in an acceptable range for ease of consumption and/or fortextural matching with the gummy composition. Likewise, lubricantsand/or hydrophobic diluents and/or processing aids may be included tomodify the texture as desired.

In some embodiments, a second composition substantially in the form of achew can be compressed to a hardness of about 2 Kp to about 30 Kp, about6 Kp to about 20 Kp, or about 10 Kp to about 18 Kp. A chewy form mayalso be characterized in relation to elasticity. For example, a chewyform may exhibit elastic or viscoelastic properties, particularly whenin a hydrated form.

A composition prepared to be in a chewy form can comprise about 10% toabout 60%, about 12% to about 50%, or about 15% to about 45% w/w of theone or more bulking agents (e.g., one or more saccharides or saccharidederivatives or other equivalent materials otherwise described herein). Achewy composition also can comprise about 5% to about 60%, about 10% toabout 50%, or about 15% to about 45% w/w of the one or more hydrophilicpolymers. One or more processing aids may be present in an amount ofabout 0.05% to 5% w/w. In some embodiments, a composition in a chewyform can include one or more active agents in an amount of 0.1% to about60%, about 1% to about 55%, or about 5% to about 50% w/w.

In an exemplary embodiment, a multicomponent dosage form may include acomposition in a chewy form having the following composition: about 10%to about 60% w/w of the one or more bulking agents, about 5% to about60% w/w of the one or more hydrophilic polymers, about 0.05% to about 5%of one or more processing aids, and about 0.1% to about 60% w/w of theone or more active ingredients

In a further exemplary embodiment, a multicomponent dosage form mayinclude a composition in a chewy form having the following composition:about 20% to about 60% w/w of one or more bulking agents, about 20% toabout 60% w/w of the one or more hydrophilic polymers, about 0.1% to 3%of one or more processing aids, and about 1% to about 40% w/w of one ormore active ingredients.

In one or more embodiments, a multicomponent dosage form according tothe present disclosure can include a second composition that isconfigured to provide a soft and/or smooth and/or rich texture. Suchcharacteristics can, for example, be provided through use of a lipidicmedium including, but not limited to, oils, fats, and compositionsformed therewith. Such characteristics also may be provided through useof one or more fat substitutes, such as various polyols (e.g.,glycerol). The disclosure thus further encompasses pre-formed units oflipidic (of lipid-based) compositions.

Lipid-based compositions (and compositions exhibiting similarproperties) can exist in a molten phase, a solid phase, or a semi-solidphase, and the transition between the phases can be achieved attemperatures wherein the lipid-based composition can provide specifictextural properties. Lipid-based compositions, however, can be formed inone or more embodiments via compression or similar molding techniques.For example, the lipid-based composition can be a soft solid at typicalroom temperatures but be substantially resistant to melting at highertemperatures to facilitate manufacturing. In other words, thelipid-based compositions can have transition temperatures so that thecomposition will remain substantially solid while being combined with aheated gummy composition. The lipid based compositions can be configuredto be a substantially homogeneous mixture of the lipid and the furtheringredients. For example, solids may be homogeneously dispersed in thelipid base.

Suitable lipidic materials for use in forming such compositions includefats derived from vegetables, nuts, seeds, and the like. Non-limitingexamples of suitable lipidic materials include fats derived from one ormore of the following: cocoa, almonds, cashews, hazelnuts, macadamianuts, peanuts, pecans, pistachios, walnuts, pumpkin seeds, sesame seeds,soybeans, rapeseed, corn, safflower seeds, and the like. Lipid basedcompositions can comprise a lipidic material in an amount of about 10%to about 60%, about 12% to about 55%, or about 15% to about 50% w/w.Specific, non-limiting examples of lipid based materials that may beused in preparing a composition as described herein include chocolateswith any cocoa concentration (e.g., milk chocolate, dark chocolate,white chocolate), peanut butter, and the like. Such materials typicallywill include additional components, such as sugar, salt, other oils, andthe like.

Compositions with a lipid base can include one or more furthercomponents. For example, one or more dairy components may be utilized,including fats, proteins, and/or sugars derived from cow milk, goatmilk, and the like.

In one or more embodiments, the lipid based composition can include oneor more bulking agents as described, particularly on or more saccharidesor saccharide derivatives. For example, the composition can compriseabout 10% to about 60%, about 12% to about 55%, or about 15% about 50%w/w of the one or more bulking agents.

The lipidic composition can comprise one or more active ingredients. Forexample, active ingredients may be present in concentration of about0.1% to about 60%, about 1% to about 55%, or about 5% to about 50% w/w.

The compositions may likewise include a component of solids (i.e., whichremain solid at temperatures above the melting temperature of the lipidused as the base material). Active ingredients may be solids present inthe composition. Cocoa solids, milk solids, nut solids, seed solids, andthe like are further examples of solids that may be present.

A lipidic composition can take on a variety of forms. For example, thecomposition may be a dispersion, an emulsion, a solution, a mixture, orthe like. In some embodiments, the composition may include one or moreingredients useful to stabilize the composition and/or facilitateformation of a substantially homogeneous state. Emulsifiers (e.g.,lecithin, monoglycerides, and the like) may be used, and suitableemulsifiers that are generally recognized as safe for products consumedby humans can be found in 21 CFR 178.3400.

Lipid based compositions can be made directly into the final form forcombination with the gummy composition. In some embodiments, a mass ofthe lipid based composition can be formed as a solid and thengranulated. The particulate material may then be compressed into a finaldesired shape (e.g., pellets) or plasticized, such as by low shearmixing of the material. In some embodiments, the lipid based materialmay be provided in a molten condition and molded into specific forms orshapes.

Lipid based compositions can be particularly useful as carriers foractive agents that may be prone to degradation if provided in othertypes of compositions. For example, beneficial bacteria that are watersensitive may be substantially enclosed in a lipid based composition soas to remain active until consumer ingestion. Likewise, heat and/orlight sensitive active agents may benefit from being present in thelipid based composition, which can be provided in a substantially opaquecolor and which can be formed under conditions with significantly coolertemperatures compared to the manufacture of a gummy composition. Waterreactive chemicals (e.g., bicarbonate) also can benefit by beingprovided within the hydrophobic, lipid based composition.

Units in a chewy or lipid based from for use in a multicomponent dosageof the present disclosure can have a variety of sizes. Such units, forexample, can have a maximum dimension of about 1 mm to about 12 mm,about 2 mm to about 10 mm, or about 3 mm to about 8 mm. In someembodiments, the unit can be substantially spherical, and the notedmaximum dimension can be a diameter of the unit. In other embodiments,the unit can have a maximum dimension as noted (e.g, a length or width)and can have a thickness that is less than the maximum dimension. Forexample, the unit can have a length or width as noted above, and have athickness that is about 10% to about 95%, about 15% to about 85%, orabout 25% to about 75% of the maximum dimension.

In one or more embodiments, the second component can be a solid shellthat defines a hollow interior. Non-limiting examples of solid shelldosing units include hard gelatin capsules and soft gelatin capsules.The solid shell itself may include an active ingredient. An activeingredient may be included in the hollow interior of the solid shell.The hollow interior additionally, or alternatively, may include any oneor more of a variety of compositions, including flavors, materialsproviding warming sensations, materials providing cooling sensations,materials providing tingling sensations, and materials configured toreact with other materials in the multicomponent dosage form to providean specific organoleptic sensation.

In one or more embodiments, the multicomponent dosage forms of thepresent disclosure can be particularly beneficial in light of the goodstability provided by the second compositions that make themparticularly suitable for combination with the gummy compositions. Goodstability can be useful where the second composition includes an activeingredient. Such improved stability can be characterized in someembodiments in relation to the ability of the core composition to resistwater absorption. Such stability of the presently disclosed corecompositions is illustrated in the Examples appended hereto. Testconditions for evaluating stability in relation to resisting waterabsorption are found in Guidance for Industry Q1A(R2) Stability Testingof New Drug Substances and Products (November 2003, Revision 2), whichguidelines are established by the U.S. Department of Health and HumanServices, Food and Drug Administration, Center for Drug Evaluation andResearch (CDER), and Center for Biologics Evaluation and Research(CBER).

In some embodiments, compositions in the form of a tablet, minitab, orthe like as described herein can exhibit a particularly level ofstability as measured separate from a gummy composition. For example, atabletted composition can be water stable such that, separate fromanother composition (e.g., separate from a gummy composition), thetabletted composition absorbs less than about 5% by weight of water(based on the weight of the tabletted composition) over a time of 14days at a temperature of 40° C. and a relative humidity of 75%. Suchstability exemplifies the ability of the tabletted composition to resistwater uptake from the gummy composition when the tabletted compositionis combined with the gummy composition particularly, for example, inembodiments wherein one or more tabletted compositions may be present asone or more cores surrounded by a gummy outer layer or shell. Stabilitycan also relate to the ability of the tabletted composition to resistdegradation in relation to an active ingredient included therein. Insome embodiments, for example, a tabletted composition can be stablesuch that the active ingredient exhibits substantially no degradationwhen the tabletted composition is stored for a time of 20 days at atemperature of 40° C. and a relative humidity of 75%.

Compositions in that are substantially in the form of a chew likewisecan exhibit good stability. For example, a chewy composition asdescribed herein can be water stable such that, separate from anothercomposition (e.g., separate from a gummy composition), the chewycomposition absorbs less than about 10% by weight of water (based on theweight of the chewy composition) over a time of 5 days at a temperatureof 40° C. and a relative humidity of 75%. As above, chewy compositionsas described herein also can be useful as stable carriers for activeingredients. For example, a chewy composition as described herein can bestable such that the active ingredient in the chewy composition exhibitssubstantially no degradation when the chewy composition is stored for atime of 11 days at a temperature of 40° C. and a relative humidity of75%.

Still further, lipid based compositions as described also can providegood stability, particularly in relation to maintaining the integrity ofan active ingredient. For example, in some embodiments, a lipid basedcomposition as described herein can be stable such that, after beingstored for a time of 28 days at a temperature of 25° C. and a relativehumidity of 60%, the lipid based composition comprises less than about0.1% by weight of active ingredient degradation products relative to theweight of the active ingredient. In further embodiments, the lipid basedcomposition can be stable such that, after being stored for a time of 28days at a temperature of 50° C. and a relative humidity of 60%, thelipid based composition comprises less than about 2% by weight of activeingredient degradation products relative to the weight of the activeingredient.

The use of multiple compositions for delivery of an active ingredientcan be particularly beneficial in that a variety of tastes andorganoleptic characteristics can be provided while simultaneouslyproviding for stability of the active ingredient. In some embodiments,stability of one or more elements of a multicomponent dosage form may beincreased through inclusion of a barrier element. Such barrier elementcan particularly be adapted to minimize the ingress/migration of waterfrom one composition to the other composition (e.g., from the gummycomposition into the second composition that may be in physical contactwith the gummy composition and particularly may be at least partiallysurrounded by the gummy composition. This can be particularly beneficialto improve stability in long-term storage. The barrier element may bepresent as one or more intermediate layers configured tocompartmentalize a unit of one composition (e.g., a core) from the gummycomposition (e.g., a shell).

A barrier layer may partially surround, substantially surround, orcompletely surround a unit of a composition as described herein. Forexample, a tablet, a chew, or a lipid based composition may bepartially, substantially, or completely separated from a gummycomposition via a barrier component. In some embodiments, a plurality ofbarrier components (e.g., layers or films) may be used.

FIG. 9 illustrates a multicomponent dosage form 90 that comprises agummy composition 92, which is substantially a shell surrounding asecond composition 94, which is substantially a core. The secondcomposition 94 is separated from the gummy composition 92 with a barrier97 that functions substantially as a layer that separates the gummycomposition from the second composition to substantially prevent orcompletely prevent water ingress from the gummy composition to thesecond composition. Likewise, returning to FIG. 6, one or both of layer63 and layer 65 may function as a barrier in this regard. Anintermediate layer may be utilized as a barrier around each individualcore that may be present in a multicomponent dosage form. In otherembodiments, two or more of a plurality of cores present in amulticomponent dosage form may be substantially surrounded by a singlebarrier element.

In some embodiments, further compartmentalization of the activeingredient(s) may be provided. For example, in addition to separatingthe active ingredient from the gummy composition by providing the activeingredient in a separate composition, the active ingredient may also bein an encapsulated form. Alternatively, the entire composition in whichthe active ingredient is included may be in an encapsulated form. Forexample, a composition including the active ingredient may be providedsubstantially in a unit form as described herein, may be in particulateform, may be in the form of microparticles or nanoparticles, and thecomposition may be encapsulated (e.g., encapsulated chews, encapsulatedlipid based units, encapsulated minitabs, encapsulated particles,encapsulated microparticles, or encapsulated nanoparticles).

Active ingredients and/or compositions including active ingredients maybe encapsulated utilizing any encapsulating technology known in the art.For example, microcapsules can be formed using any of various chemicalencapsulation techniques such as solvent evaporation, solventextraction, organic phase separation, interfacial polymerization, simpleand complex coacervation, in-situ polymerization, liposomeencapsulation, and nanoencapsulation. Alternatively, physical methods ofencapsulation could be used, such as spray coating, pan coating, fluidbed coating, annular jet coating, spinning disk atomization, spraycooling, spray drying, spray chilling, stationary nozzle coextrusion,centrifugal head coextrusion, or submerged nozzle coextrusion.

Regardless of the encapsulation methodology employed, the outer wall orshell material and solvents used to form the capsules can vary. Classesof materials that are typically used as wall or shell materials includeproteins, polysaccharides, starches, waxes, fats, natural and syntheticpolymers, and resins. Exemplary materials for use in themicroencapsulation process used to form the microcapsules includegelatin, acacia (gum arabic), polyvinyl acetate, potassium alginate,carob bean gum, potassium citrate, carrageenan, potassiumpolymetaphosphate, citric acid, potassium tripolyphosphate, dextrin,polyvinyl alcohol, povidone, dimethylpolysiloxane, dimethyl silicone,refined paraffin wax, ethylcellulose, bleached shellac, modified foodstarch, sodium alginate, guar gum, sodium carboxymethylcellulose,hydroxypropyl cellulose, sodium citrate, hydroxypropylmethylcellulose,sodium ferrocyanide, sodium polyphosphates, locust bean gum,methylcellulose, sodium trimetaphosphate, methyl ethyl cellulose, sodiumtripolyphosphate, microcrystalline wax, tannic acid, petroleum wax,terpene resin, tragacanth, polyethylene, xanthan gum, and polyethyleneglycol.

Microcapsules are commercially available, and exemplary types ofmicrocapsule technologies are of the type set forth in Gutcho,Microcapsules and Microencapsulation Techniques (1976); Gutcho,Microcapsules and Other Capsules Advances Since 1975 (1979); Kondo,Microcapsule Processing and Technology (1979); Iwamoto et al., AAPSPharm. Sci. Tech. 2002 3(3): article 25; U.S. Pat. No. 5,004,595 toCherukuri et al.; U.S. Pat. No. 5,690,990 to Bonner; U.S. Pat. No.5,759,599 to Wampler et al.; U.S. Pat. No. 6,039,901 to Soper et al.;U.S. Pat. No. 6,045,835 to Soper et al.; U.S. Pat. No. 6,056,992 to Lew;U.S. Pat. No. 6,106,875 to Soper et al.; U.S. Pat. No. 6,117,455 toTakada et al.; U.S. Pat. No. 6,482,433 to DeRoos et al.; and U.S. Pat.No. 6,929,814 to Bouwmeesters et al.; each of which is incorporatedherein by reference.

Embodiments of the present disclosure are further illustrated by thefollowing examples, which are set forth to illustrate the presentlydisclosed subject matter and are not to be construed as limiting. Theexamples describe exemplary formulations for rapidly disintegrating corecompositions and exemplary formulations for minitab core compositions.The examples further describe stability testing for the corecompositions. The examples also provide exemplary formulations for gummybases useful as the outer composition surrounding a core.

Example 1—Rapidly Disintegrating Tablet Compositions

Exemplary formulations according to the present disclosure for rapidlydisintegrating tablet compositions are shown in TABLE 1 and TABLE 2.Each exemplary tablet was prepared to include 80 mg of acetaminophen asthe active ingredient using 86.96 mg of ACTIMASK® acetaminophen. TheLUDIFLASH® used in formulation 14CF13/042 is co-processed mannitol,crospovidone, and polyvinyl acetate. The PEARLITOL® Flash used informulation 14CF13/043 is co-processed mannitol and starch. ThePHARMABURST® 500 used in formulation 14CF13/044 is co-processedmannitol, sorbitol, crospovidone, and silica combined with aspartame andmagnesium stearate. The PROSOLV® ODT used in formulation 14CF13/045 isco-processed microcrystalline cellulose, colloidal silicon dioxide,mannitol, fructose, and crospovidone.

To prepare each formulation, the compressible carrier was weighed andscreened before being placed into a blending vessel (Turbula T2Fblender). The active ingredient was added to the blending vessel, andthe components were blended for 10 minutes. The sodium stearyl fumaratelubricant was added to the blended components while sifting through a500 μm sieve, and the mixture was blended for 2 minutes. The finalmixture was compressed using a Manesty F single station tablet press tothe target tablet weight and hardness.

TABLE 1 mg/tablet (% w/w) Formulation Number Ingredient Function14CF13/042 14CF13/043 14CF13/044 14CF13/045 Acetaminophen Taste-masked86.96 mg 86.96 mg 86.96 mg 86.96 mg ACTIMASK ® (92%) API (29% w/w) (29%w/w) (29% w/w) (29% w/w) LUDIFLASH ® Compressible 210.4 mg — — — carrier(70% w/w) PEARLITOL ® Flash Compressible — 210.4 mg — — carrier (70%w/w) PHARMABURST ® Compressible — — 210.4 mg — 500 carrier (70% w/w)PROSOLV ® ODT Compressible — — — 210.4 mg carrier (70% w/w) SodiumStearyl Lubricant  3.0 mg  3.0 mg  3.0 mg  3.0 mg Fumarate  (1% w/w) (1% w/w)  (1% w/w)  (1% w/w)

TABLE 2 mg/tablet (% w/w) Formulation Number Ingredient Function14CF13/046 14CF13/047 14CF13/048 14CF13/049 14CF13/050 AcetaminophenTaste-  86.96 mg  86.96 mg  86.96 mg  86.96 mg  86.96 mg ACTIMASK ®masked API (29% w/w) (29% w/w) (29% w/w) (29% w/w) (29% w/w) (92%)Mannitol Compressible 180.04 mg 180.04 mg 180.04 mg 180.04 mg 180.04 mgcarrier (60% w/w) (60% w/w) (60% w/w) (60% w/w) (60% w/w) CroscarmelloseDisintegrant  30.0 mg — — —  15.0 mg sodium (10% w/w) (5% w/w) Sodiumstarch Disintegrant —  30.0 mg — —  15.0 mg glycolate (10% w/w) (5% w/w)Crospovidone Disintegrant — —  30.0 mg — — (10% w/w) CrospovidoneDisintegrant — —  30.0 mg — (super fine) (10% w/w) Sodium StearylLubricant   3.0 mg   3.0 mg   3.0 mg   3.0 mg   3.0 mg Fumarate (1% w/w)(1% w/w) (1% w/w) (1% w/w) (1% w/w)

Example 2—Weight Stability of Rapidly Disintegrating Tablet Compositions

The formulations shown in TABLE 1 and TABLE 2 were weighed at the timefor tablet formation. The tablets were stored in open conditions at atemperature of 40° C. and a relative humidity of 75% for 14 days. Thetablets were weighed, and the percent change in weight was recorded,with any increase in weight being attributed to uptake of ambient water.The results are provided in FIG. 10. As seen therein the tablets onaverage exhibited a water weight gain of less than 1.4%. Formulations14CF13/042 and 14CF13/043 demonstrated no weight gain while formulation14CF13/044 disintegrated within 5 days.

Example 3—Chemical Degradation Analysis of Acetaminophen

Formulations 14CF13/042, 14CF13/073, 14CF13/049, and 14CF13/050 wereevaluated by high performance liquid chromatography (HPLC) after openstorage for 20 days at a temperature of 40° C. and 75% relativehumidity. The samples were tested against tablets of identicalformulation stored under lab conditions which are typically 20-25° C.and 55-65% relative humidity. The lab stored tablets were controls forthe samples that were stored open at the stress storage condition of 40°C./75% RH In all four samples, no degradation was observed in that thechromatogram for the openly stored sample was identical to thechromatogram for the lab-stored tablet.

Example 4—Minitab Compositions

Exemplary formulations according to the present disclosure for minitabcompositions are shown in TABLE 3 and TABLE 4. Each exemplary tablet wasprepared to include 80 mg of acetaminophen as the active ingredientusing 86.96 mg of ACTIMASK® acetaminophen. To prepare each formulation,all ingredients except the API and the lubricant were weighed andscreened before being placed into a blending vessel (Turbula T2Fblender). The active ingredient was added to the blending vessel, andthe components were blended for 10 minutes. The lubricant was added tothe blended components while sifting through a 500 μm sieve, and themixture was blended for 2 minutes. The final mixture was compressedusing a Manesty F single station tablet press to the target tabletweight and hardness.

TABLE 3 mg/tablet (% w/w) Formulation Number Ingredient Function14CF20/005 14CF20/006 14CF20/007 14CF20/008 Acetaminophen Taste-masked86.96 mg 86.96 mg 86.96 mg 86.96 mg ACTIMASK ® (92%) API (29% w/w) (29%w/w) (29% w/w) (29% w/w) Sorbitol Compressible 210.04 mg  — — — carrier(70% w/w) Mannitol Compressible — 210.04 mg  — — carrier (70% w/w)Isomalt Compressible — — 210.04 mg  — carrier (70% w/w) DextratesCompressible — — — 210.04 mg  carrier (70% w/w) Sodium Stearyl Lubricant 3.0 mg  3.0 mg  3.0 mg  3.0 mg Fumarate  (1% w/w)  (1% w/w)  (1% w/w) (1% w/w)

TABLE 4 mg/tablet (% w/w) Formulation Number Ingredient Function14CF20/009 14CF20/010 14CF20/011 14CF20/012 Acetaminophen Taste-masked 86.96 mg  86.96 mg  86.96 mg  86.96 mg ACTIMASK ® (92%) API (29% w/w)(29% w/w) (29% w/w) (29% w/w) Mannitol Compressible 105.02 mg — 105.02mg 210.04 mg carrier (35% w/w) (35% w/w) (70% w/w) DextratesCompressible — 105.02 mg — — carrier (35% w/w) Xylitol Compressible105.02 mg 105.02 mg 105.02 mg — carrier (35% w/w) (35% w/w) (35% w/w)Sodium Stearyl Lubricant   3.0 mg   3.0 mg — — Fumarate  (1% w/w)  (1%w/w) Magnesium stearate Lubricant — —   3.0 mg   3.0 mg  (1% w/w)  (1%w/w)

Example 5—Weight Stability of Minitab Compositions

The formulations shown in TABLE 3 and TABLE 4 were weighed at the timefor tablet formation. The tablets were stored in open conditions at atemperature of 40° C. and a relative humidity of 75% for 7 days. Thetablets were weighed on days 1, 3, 6, 7, and the change in weight wasrecorded, with any increase in weight being attributed to uptake ofambient water. The results are provided in FIG. 11. Formulations14CF20/006, 14CF20/007, 14CF20/008, and 14CF20/012 demonstrated noweight gain over a period of 7 days. Formulation 14CF20/011disintegrated after 3 days. Formulation 14CF20/009 disintegrated after 1day. Formulations 14CF20/005 and 14CF20/010 disintegrated in less thanone day.

Example 6—Chemical Degradation Analysis of Acetaminophen in Minitabs

Formulations 14CF20/006, 14CF20/007, 14CF20/008, and 14CF20/012 wereevaluated by high performance liquid chromatography (HPLC) after openstorage for 14 days at a temperature of 40° C. and 75% relativehumidity. The samples were tested against tablets of identicalformulation stored under lab conditions which are typically 20-25° C.and 55-65% relative humidity. The lab stored tablets were controls forthe samples that were stored open at the stress storage condition of 40°C./75% RH. In three of the samples, no degradation was observed in thatthe chromatogram for the openly stored sample was identical to thechromatogram for the lab-stored tablet. In formulation 14CF20/008, anadditional peak was observed on the chromatogram indicating the presenceof a possible degradation product at an amount of 0.3% relative to theacetaminophen.

Example 7—Chewy Compositions

Exemplary formulations according to the present disclosure forcompositions having a chewy texture are shown in TABLE 5 and TABLE 6.Each exemplary chewy composition was prepared to include 80 mg ofacetaminophen as the active ingredient using 86.96 mg of ACTIMASK®acetaminophen.

To prepare each formulation, the components (except any lubricant used)were weighed and screened before being placed into a blending vessel(Turbula T2F blender). The active ingredient was added to the blendingvessel, and the components were blended for 10 minutes. The sodiumstearyl fumarate lubricant was added to the blended components whilesifting through a 500 μm sieve, and the mixture was blended for 2minutes. The final mixture was compressed using a Manesty F singlestation tablet press to the target tablet weight and hardness.

TABLE 5 mg/tablet (% w/w) Formulation Number Ingredient Function14CF21/023 14CF21/024 14CF21/025 14CF21/026 Acetaminophen Taste-masked86.96 mg   86.96 mg   86.96 mg   86.96 mg   ACTIMASK ® (92%) API (29%w/w) (29% w/w) (29% w/w) (29% w/w) Sodium alginate Hydrophilic 60 mg 60mg 60 mg 60 mg polymer (20% w/w) (20% w/w) (20% w/w) (20% w/w) PectinHydrophilic 60 mg 60 mg 60 mg 60 mg polymer (20% w/w) (20% w/w) (20%w/w) (20% w/w) Dextrin Bulking agent 56.44 mg   86.44 mg   — — (19% w/w)(29% w/w) Mannitol Bulking agent — — 56.44 mg   — (19% w/w) MaltodextrinBulking agent — — — 56.44 mg   (19% w/w) Calcium carbonate Alginate 30mg — 30 mg 30 mg crosslinker (10% w/w) (10% w/w) (10% w/w) Citric acidAcidulant 3.0 mg  3.0 mg  3.0 mg  3.0 mg   (1% w/w)  (1% w/w)  (1% w/w) (1% w/w) Sucralose Sweetener 0.6 mg  0.6 mg  0.6 mg  0.6 mg  (0.2%w/w)  (0.2% w/w)  (0.2% w/w)  (0.2% w/w)  Sodium stearyl Lubricant 3.0mg  3.0 mg  3.0 mg  3.0 mg  fumarate  (1% w/w)  (1% w/w)  (1% w/w)  (1%w/w)

TABLE 6 mg/tablet (% w/w) Formulation Number Ingredient Function14CF21/027 14CF21/028 14CF21/029 14CF21/030 14CF21/031 AcetaminophenTaste-  86.96 mg  86.96 mg  86.96 mg  86.96 mg  86.96 mg ACTIMASK ®masked API (29% w/w) (29% w/w) (29% w/w) (29% w/w) (29% w/w) (92%)Sodium Hydrophilic — — —    30 mg    30 mg alginate polymer (10% w/w)(10% w/w) Pectin Hydrophilic    30 mg    30 mg    30 mg    30 mg    30mg polymer (10% w/w) (10% w/w) (10% w/w) (10% w/w) (10% w/w) AcaciaHydrophilic    60 mg    60 mg    60 mg    30 mg    30 mg polymer (20%w/w) (20% w/w) (20% w/w) (10% w/w) (10% w/w) Dextrin Bulking 116.44 mg —— — — agent (39% w/w) Mannitol Bulking — — — 116.44 mg    60 mg agent(39% w/w) (20% w/w) Isomalt Bulking — — 116.44 mg —  56.44 mg agent (39%w/w) (19% w/w) Maltodextrin Bulking — 116.44 mg — — — agent (39% w/w)Citric acid Acidulant   3.0 mg   3.0 mg   3.0 mg   3.0 mg   3.0 mg (1%w/w) (1% w/w) (1% w/w) (1% w/w) (1% w/w) Sucralose Sweetener   0.6 mg  0.6 mg   0.6 mg   0.6 mg   0.6 mg (0.2% w/w) (0.2% w/w) (0.2% w/w)(0.2% w/w) (0.2% w/w) Sodium stearyl Lubricant   3.0 mg   3.0 mg   3.0mg   3.0 mg   3.0 mg fumarate (1% w/w) (1% w/w) (1% w/w) (1% w/w) (1%w/w)

Example 8—Weight Stability of Chewy Compositions

The formulations shown in TABLE 5 and TABLE 6 were weighed at the timefor tablet formation. The tablets were stored in open conditions at atemperature of 40° C. and a relative humidity of 75% for 5 days, and thechange in weight was recorded, with any increase in weight beingattributed to uptake of ambient water. The results are provided in FIG.12.

Example 9—Chemical Degradation Analysis of Acetaminophen in ChewyCompositions

Formulations 14CF21/025, 14CF21/026, 14CF21/029, and 14CF21/030 wereevaluated by high performance liquid chromatography (HPLC) after openstorage for 11 days at a temperature of 40° C. and 75% relativehumidity. The samples were tested against tablets of identicalformulation stored under lab conditions which are typically 20-25° C.and 55-65% relative humidity. The lab stored tablets were controls forthe samples that were stored open at the stress storage condition of 40°C./75% RH. No degradation was observed in any of the testedsamples—i.e., the chromatogram for the openly stored sample wasidentical to the chromatogram for the lab-stored tablet.

Example 10—Lipid-Based Compositions

Exemplary formulations according to the present disclosure forlipid-based compositions are shown in TABLE 7. Each exemplarylipid-based composition was prepared to include one of the followingactive ingredients: vitamin C; pantothenic acid; folic acid;acetylsalicylic acid; loratadine; acetaminophen; or ibuprofen.

Each formulation included a combination of white chocolate, milled sugar(sucrose), and corn starch. The white chocolate was a commerciallyavailable composition having the following ingredients: 20-30% by weightmilk solids; 35-55% by weight sugars; 25-45% by weight total fats; and0.3-1% by weight legally permitted emulsifiers. Although white chocolatewas used, other chocolates (e.g., milk chocolate, dark chocolate, etc.)as also contemplated. To prepare each formulation, the components wereweighed and screened before being placed into a blending vessel. Theactive ingredient was added to the blending vessel, and the componentswere blended. The final mixture was formed into a unitary structurehaving a mass of 250 mg.

TABLE 7 mg/unit (% w/w) Formulation Number Ingredient 222121 222122222123 222124 222125 222126 222127 222128 White Chocolate 85 76.8 76.782.0 62.1 83.6 62.3 70.9 Milled Sugar 15 13.6 13.5 14.5 11.0 14.7 11.012.5 Corn Starch 5 4.5 4.5 4.8 3.6 4.9 3.6 4.2 Vitamin C — 9.6 — — — — —— Pantothenic acid — — 9.8 — — — — — Folic acid (10% on — — — 3.53 — — —— dextrose Acetylsalicylic acid — — — — 27.00 — — — Loratadine — — — — —1.67 — Acetaminophen — — — — — — 26.67 — Ibuprofen — — — — — — — 16.57Color/Flavor q.s q.s q.s q.s q.s q.s q.s q.s Water to 100 to 100 to 100to 100 to 100 to 100 to 100 to 100

Example 11—Gummy Composition

A gummy base suitable for use as an outer composition in an oral,chewable dosage form was prepared using the components shown in TABLE 8.A first solution was formed by combining the gelatin, sucrose, and waterat 60° C. A second solution was formed by combining the glucose syrupsand sucrose and warming to 60° C. The first and second solutions werecombined, and the calcium carbonate was added with mixing. The blendedmixture (slurry) was held at 55-60° C. in a batch tank. The slurry washeated to 104° C. and flash cooled to 90° C. to reduce solids to 82/84Brix. Thereafter, natural flavors and colors were added along withcitric acid, and the mixture was placed into molds.

TABLE 8 Hydrocolloid System Component Amount (% w/w) Gelatin 250 bloom5.89 Pectin CS502 0.15 Sucrose 2.46 Water (60° C.) 15.17 Glucose Syrup63 DE 28.00 Glucose Syrup 43 DE 15.00 Sucrose 25.54 Calcium carbonate6.70 Color/Flavor 1.04 Citric Acid 0.05

Example 12—Gummy Composition

A gummy base suitable for use as an outer composition in an oral,chewable dosage form was prepared using the components shown in TABLE 9.The pectin and carragennan were mixed with the dispersing sucrose andhydrated in the water at 80° C. Separately, the glucoses were heated inthe dispersing water to 90° C. The sucrose was added to theglucose/water mixture and heated to 90-100° C. The pectin/carragennanmixture was added to the glucose mixture to form a slurry. The slurrywas heated to 104° C. and flash cooled to 90° C. to reduce solids to82/84 Brix Thereafter, natural flavors and colors were added along withcitric acid, and the final composition was deposited into molds.

TABLE 9 Hydrocolloid System Component Amount (% w/w) Pectin CS502 2.00Carrageenan 310C 0.50 Sucrose (to disperse) 3.00 Water 20.00 Water (todisperse) 4.50* Glucose 42 16.00 Glucose 63 29.00 Sucrose 24.00Flavor/Color/Acid 5.50 *Removed during processing

Example 13—Preparation of Oral, Chewable Dosage Form

An oral, chewable dosage form was prepared by forming a core compositionas described herein and forming a gummy base as described herein. Aportion of the gummy base composition was deposited into a mold to forma base (or cap) of the dosage form. The core was placed on top of thedeposited gummy base portion. The remaining gummy base mixture was addedto the mold to cover and fully surround the core. The dosage form wasthen cooled to a defined profile to allow for a controlled setting rate.

Many modifications and other embodiments of the inventions set forthherein will come to mind to one skilled in the art to which theseinventions pertain having the benefit of the teachings presented in theforegoing descriptions. Therefore, it is to be understood that theinventions are not to be limited to the specific embodiments disclosedand that modifications and other embodiments are intended to be includedwithin the scope of the appended claims. Although specific terms areemployed herein, they are used in a generic and descriptive sense onlyand not for purposes of limitation.

1. A chewable, multicomponent composition for oral administration, themulticomponent composition comprising: a first component that is ahydrocolloid system comprising about 70% to about 94% w/w of one or morehydrophilic bulking agents, about 1% to about 20% w/w of one or morehydrophilic, long chain polymers, and about 5% to about 35% w/w of awater source, the first component being in the form of a gel; a secondcomponent that is in the form of a particulate material or is apre-formed solid unit or plurality of pre-formed solid units; and anactive ingredient; wherein the first component substantially surroundsthe second component.
 2. (canceled)
 3. The multicomponent composition ofclaim 1, further comprising a third component configured as a layerbetween the first component and the second component.
 4. Themulticomponent composition of claim 3, wherein the third component isconfigured as a barrier layer that substantially prevents passage ofwater between the first component and the second component.
 5. Themulticomponent composition of claim 1, wherein one or more of thefollowing conditions is met: the active ingredient is included in thesecond component; the active ingredient is included in the firstcomponent; the active ingredient is in an encapsulated form; the gummycomposition is elastic or viscoelastic; the multicomponent compositionfurther comprises an outer layer surrounding the first component and thesecond component.
 6. The multicomponent composition of claim 1, whereinthe active ingredient is a natural or synthetic substance that isrecognized as being beneficial to human health and is selected from thegroup consisting of non-steroidal anti-inflammatory drugs (NSAIDs),analgesics, antihistamines, decongestants, antitussives, expectorants,sleep aids, antibiotics, laxatives, anti-diarrheals, anthelmintics,antacids, vitamins, minerals, phytonutrients, fiber, fatty acids, aminoacids, polypeptides, botanicals, herbs, prebiotics, probiotics, andcombinations thereof.
 7. (canceled)
 8. The multicomponent composition ofclaim 7, wherein one or more of the following conditions is met: the oneor more hydrophilic bulking agents includes one or more saccharides orsaccharide derivatives; the one or more hydrophilic bulking agentsincludes one or more hydrogenated carbohydrates; the one or morehydrophilic bulking agents includes one or both of sugar solids andgranulated sugar; the one or more hydrophilic bulking agents includesglucose, sucrose, and sorbitol.
 9. The multicomponent composition ofclaim 1, wherein the second composition comprises one or moreingredients selected from the group consisting of saccharides,saccharide derivatives, lipids, cellulosic polymers, cellulosic polymerderivatives, inorganic salts, and combinations thereof.
 10. Themulticomponent composition of claim 1, wherein the second composition isa pre-formed solid unit in the form of one or more of a tablet, acaplet, a hard shell capsule, a soft shell capsule, a microcapsule, anda pastille.
 11. The multicomponent composition of claim 1, wherein thesecond composition is a pre-formed tablet having a hardness of about 2Kp to about 35 Kp.
 12. The multicomponent composition of claim 11,wherein one or more of the following conditions is met: the pre-formedtablet is orally disintegrable or dissolvable; the pre-formed tablet hasa hardness of about 4 Kp to about 20 Kp; the pre-formed tablet, prior tocombination with the first component, is fracturable and has abrittleness index of about 0.5 to about 0.95.
 13. The multicomponentcomposition of claim 11, wherein the pre-formed tablet comprises about5% to about 80% w/w of one or more bulking agents, about 0.1% to about15% w/w of one or more disintegrants, about 0.05% to about 5% w/w of oneor more processing aids, and the active ingredient in an amount of about0.1% to about 60% w/w.
 14. The multicomponent composition of claim 11,wherein one or both of the following conditions is met: the pre-formedtablet is stable such that the active ingredient exhibits substantiallyno degradation when the core composition is stored for a time of 20 daysat a temperature of 40° C. and a relative humidity of 75%; thepre-formed tablet is stable such that, separate from the firstcomponent, the pre-formed tablet absorbs less than about 5% by weight ofwater (based on the weight of the tabletted composition) over a time of14 days at a temperature of 40° C. and a relative humidity of 75%. 15.The multicomponent composition of claim 11, wherein the pre-formedtablet has a diameter of about 6 mm to about 12 mm and a thickness ofabout 0.5 mm to 8 mm; or wherein the pre-formed tablet has a diameter ofabout 2 mm to about 10 mm and a thickness of about 0.5 mm to 6 mm. 16.The multicomponent composition of claim 1, wherein the secondcomposition is a pre-formed unit of a chewy composition having ahardness of about 4 Kp to about 20 Kp.
 17. The multicomponentcomposition of claim 16, wherein the pre-formed unit of the chewycomposition comprises about 10% to about 60% w/w of one or more bulkingagents, about 5% to about 60% w/w of one or more hydrophilic polymers,about 0.05% to 5% of one or more processing aids, optionally one or moredisintegrants, and the active agent in an amount of about 0.1% to about60% w/w.
 18. The multicomponent composition of claim 16, wherein one orboth of the following conditions is met: the pre-formed unit of thechewy composition is water stable such that, separate from the firstcomponent, the chewy composition absorbs less than about 10% by weightof water (based on the weight of the chewy composition) over a time of 5days at a temperature of 40° C. and a relative humidity of 75%; thepre-formed unit of the chewy composition is stable such that the activeingredient exhibits substantially no degradation when the chewycomposition is stored for a time of 11 days at a temperature of 40° C.and a relative humidity of 75%.
 19. The multicomponent composition ofclaim 16, wherein the pre-formed unit of the chewy composition has adiameter of about 6 mm to about 12 mm and a thickness of about 0.5 mm to8 mm.
 20. The multicomponent composition of claim 1, wherein the secondcomposition is a pre-formed unit of a lipidic composition that comprisesone or more lipidic materials and one or more bulking agents.
 21. Themulticomponent composition of claim 20, wherein the one or more lipidicmaterials are selected from the group consisting of vegetable fats, nutfats, seed fats, and combinations thereof.
 22. (canceled)
 23. Themulticomponent composition of claim 20, wherein one or more of thefollowing conditions is met: the pre-formed unit of the lipidiccomposition comprises about 10% to about 60% w/w of the one or morelipid materials and about 10% to about 60% w/w of the one or morebulking agents; the active ingredient is present in the pre-formed unitof the lipidic composition, and wherein the pre-formed unit of thelipidic composition is stable such that, after being stored for a timeof 28 days at a temperature of 50° C. and a relative humidity of 60%,the pre-formed unit of the lipidic composition comprises less than about2% by weight of active ingredient degradation products relative to theweight of the active ingredient; the pre-formed unit of the lipidiccomposition has a diameter of about 0.5 mm to about 10 mm; the one ormore lipidic materials comprises cocoa fat. 24-25. (canceled)
 26. Themulticomponent composition of claim 1, wherein the second composition isin the form of a particulate material comprises of powders, granules,beads, or combinations thereof.
 27. (canceled)